The sequences of siRNAs used in this study.

<div><p>Decidual macrophages residing at the maternal-fetal interface have been recognized as pivotal factors for maintaining normal pregnancy; however, they are also key target cells of <i>Toxoplasma gondii</i> (<i>T</i>. <i>gondii</i>) in the pathology of <i>T</i>. <i>gondii</i>-induced adverse pregnancy. Trem2, as a functional receptor on macrophage surface, recognizes and binds various kinds of pathogens. The role and underlying mechanism of Trem2 in <i>T</i>. <i>gondii</i> infection remain elusive. In the present study, we found that <i>T</i>. <i>gondii</i> infection downregulated Trem2 expression and that Trem2<sup>-/-</sup> mice exhibited more severe adverse pregnancy outcomes than wildtype mice. We also demonstrated that <i>T</i>. <i>gondii</i> infection resulted in increased decidual macrophages, which were significantly reduced in the Trem2<sup>-/-</sup> pregnant mouse model as compared to wildtype control animals. We further described the inhibited proliferation, migration, and invasion functions of trophoblast cell by <i>T</i>. <i>gondii</i> antigens through macrophages as an "intermediate bridge", while this inhibition can be rescued by Trem2 agonist HSP60. Concurrently, Trem2 deficiency in bone marrow-derived macrophages (BMDMs) heightened the inhibitory effect of <i>Tg</i>Ag on the migration and invasion of trophoblast cells, accompanied by higher pro-inflammatory factors (IL-1β, IL-6 and TNF-α) but a lower chemokine (CXCL1) in <i>T</i>. <i>gondii</i> antigens-treated BMDMs. Furthermore, compelling evidence from animal models and <i>in vitro</i> cell experiments suggests that <i>T</i>. <i>gondii</i> inhibits the Trem2-Syk-PI3K signaling pathway, leading to impaired function of decidual macrophages. Therefore, our findings highlight Trem2 signaling as an essential pathway by which decidual macrophages respond to <i>T</i>. <i>gondii</i> infection, suggesting Trem2 as a crucial sensor of decidual macrophages and potential therapeutic target in the pathology of <i>T</i>. <i>gondii</i>-induced adverse pregnancy.</p></div>